title: Nodal promotes the generation of M2-like macrophages and downregulates the expression of IL-12.
abstract: Nodal, a member of the TGF-β superfamily, is an embryonic morphogen that is upregulated in different types of tumors. Nodal increases the tumorigenesis by inducing angiogenesis and promoting metastasis. Importantly, Nodal inhibition suppresses the growth and invasion of tumor. Since tumor-associated macrophages (TAMs) are the major infiltrating leukocytes in most cancers, we investigated whether Nodal is involved in the differentiation of TAMs. Our results revealed that Nodal inhibition in tumor microenvironment upregulated the production of IL-12 in macrophages and reversed TAMs to classically activated macrophage phenotype. In contrast, treatment with recombinant Nodal (rNodal) decreased the expression of IL-12 in murine macrophages. Furthermore, rNodal promoted macrophage polarization to an alternatively activated macrophage-like/TAM phenotype and modulated its function. These results suggest that Nodal may play an important role in macrophage polarization and downregulation of IL-12. The rescued antitumor function of TAMs via the inhibition of Nodal expression could be a new therapeutic strategy for cancer treatment.
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Ke-Fang
authors.initials: KF
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Xian-zhang
authors.initials: XZ
authors.lastname: Bu
authors.forename: Shao-Hui
authors.initials: SH
authors.lastname: Cai
authors.forename: Jun
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D063646:Carcinogenesis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D055457:Nodal Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D055457:Nodal Protein; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D018664:Interleukin-12
keywords: Cancer therapy; IL-12; M2-like macrophage; Nodal; TAMs